Reticuloendothelial block

Iron deficiency is the most common cause of resistance to erythropoietic therapy. Evaluation and treatment of iron deficiency should occur prior to initiation of erythropoietic therapy as previously discussed (see Figs. 44—1 and 44—2). Inflammation (localized or systemic infection, active inflammatory disease, or surgical trauma) is associated with defective iron utilization known as reticuloendothelial block. Reticuloendothelial block is characterized by a reduction in iron delivery from body stores to the bone marrow, and is generally refractory to iron therapy. Failure to respond to erythropoietic therapy requires evaluation of other factors causing resistance, such as infection, inflammation, chronic blood loss, aluminum toxicity, hemoglobinopathies, malnutrition, and hyperparathyroidism. Erythropoietic therapy may be continued in the infected or postoperative patient, although increased doses are often required to maintain or slow the rate of decline in Hgb/Hct. Deficiencies in folate and vitamin Bi2 should also be considered as potential causes of resistance to erythropoietic therapy, as both are essential for optimal erythropoiesis. Patients on hemodialysis or peritoneal dialysis should be routinely... 

We have shown that polymeric micelles constmcted of block copolymers of poly(ethylene oxide) (PEG) and poly(L-asparate) containing the anticancer dmg (adriamycin, ADR) selectively accumulate at solid tumor sites by a passive targeting mechanism. This is likely due to the hydrophilicity of the outer PEG chains and micellar size (<100 nm) that allow selective tissue interactions [17,18]. Polymeric micelle size ranges are tailored during polymer synthesis steps. Carefully selection of block polymer chemistry and block lengths can produce micelles that inhibit nonselective scavenging by the reticuloendothelial system (RES) and can be utilized as targetable dmg... 

Thermosensitive block copolymer nanoparticles containing doxorubicin increased cytotoxicity against Lewis lung carcinoma cells when activated by heating above the LCST [139], Chitosan was chemically conjugated to NIPAAm/vinyl laurate copolymer to enhance gene transfection in mouse myoblast cells [140]. Upon i.v. administration, poly(NIPAAm) nanoparticles are taken up by the reticuloendothelial cells of the liver and mild inflammatory and fibrotic responses are observed... 

In hemophilia A, the protein sequence of factor VIII is mutated so that it cannot be cleaved, resulting in a blocked intrinsic pathway. Therefore, tissue factor must be activated to stop bleeding (extrinsic pathway). Because the capillaries of joints and muscles are continually damaged by crushing when the surrounding bones and muscles move, they produce small amounts of RNA that activates the intrinsic path. Because there is no tissue factor at that site and the mutation of factor VIII in hemophilia A has blocked the intrinsic path, the affected subjects bleed into the joints. The pressure in the joint eventually stops the bleeding, and reticuloendothelial cells are recruited to remove the blood cells. The pain is relieved, but the joint structure is slowly destroyed and over time surviving individuals develop arthritis. 

ACD is a hypoprolrferative anemia that has traditionally been associated with infectious or inflammatory processes, tissue injury, or conditions associated with the release of proinflammatory cytokines. Alternative names include anemia of inflammation and cytokine-mediated anemia. The pathogenesis of the anemia of chronic disorders is based on three abnormalities shortened erythrocyte survival, impaired marrow response, and disturbance of iron metabolism. Pathologically, the RBCs have a shortened life span, and the bone marrow s capacity to respond to EPO is inadequate to maintain normal Hgb concentration. The cause of this defect is still uncertain, but appears to involve a block in the release of iron from the reticuloendothelial cells of the marrow. Various cytokines, such as interleukin-1, interferon-y, and tumor necrosis factor released during these illnesses may inhibit the production or action of EPO or the production of RBCs. ... 

Conticello and colleagues have studied the potential of amphiphilic diblock (AB) and triblock (ABA) elastin-like copolymers, where A is a hydrophilic and B a hydrophobic block, to reversibly self-assemble into well-defined micellar aggregates (20,30). Collapse of the hydrophobic block above Tt results in the formation of elastin-based nanoparticles. To provide diversity in the mechanical properties of the micellar structures, the amino acid sequence of the hydrophobic block was varied between plastic (VPAVG) and elastomeric (VPGVG) in nature. The hydrophilic block is designed to maintain solubility and form a protective core that prevents protein adsorption and clearance by the reticuloendothelial system. 

These molecules are continuously absorbed by the intestine. The amount of endotoxin absorbed is proportional to the size of the endotoxin pool in the lumen. The endotoxins are known to block the activity of the reticuloendothelial system and to precipitate the transition from reversible to irreversible shock. In shock, the effect of the endotoxin gives the final blow to the reticuloendothelial system, which has been damaged by hypoxia and reduced blood flow. 

Splenic factor inhibits platelet formation in bone marrow by blocking formation of megakaryocytes reticuloendothelial cells platelets... 

Gadolinium ions are highly toxic in their hydrated form [Gd(H20)g] +. In vivo, Gd + ions compete with calcium ions and block the reticuloendothelial system. To avoid this toxicity, gadolinium is complexed with an organic thermodynamically stable matrix, (see Lanthanide Complexes with Multidentate Ligands, Organometallic Chemistry Fundamental Properties, Lanthanides Coordination Chemistry) In addition, ligands that allow coordination sites for one (or more) water molecule(s) ate preferred since they increase... 

The uptake of particles has previously been thought to be the task of the reticuloendothelial cells. It could actually be shown that exogenous cholesterol enters Kupffer cells (Friedman et al. 1954) but this process does not seem to be essential for the assimilation of triglycerides nor is it quantitatively important (van den Bosch et al. 1961). Blocking the Kupffer cells by injections of colloidal carbon did not interfere with the removal of fat and its deposition in the parenchymal cells of the liver (Waddell et al. 1954). It seems to be mainly the function of the parenchymal cells to assimilate and metabolize chylomicron triglycerides (DiLxjzio 1960) whereas artifical fat emulsions are also taken up by the reticuloendothelial cells of the liver. 

Generally, the amphiphilic core/shell stmcture of polymeric micelles is formed from block polymers. Polyethylene glycol (PEG) and polyethylene oxide (PEO) are often used as the hydrophilic blocks. They have been shotvn to prevent recognition by the reticuloendothelial system and increase circulation time in vivo. As in the case of liposomes and niosomes, the grafting of specific ligand molecules on the surface of the polymeric micelles allows... 

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